Abstract3-Benzyloxy-6-formylaminotoluene (III) could not be converted by Madelung cyclization into the corresponding indole derivative. It was found, that 4-aminobutanal diethyl acetal and p-benzyloxyphenylhydrazine hydrochloride cyclize into 5-benzyloxytryptamine hydrochloride (V) in 25% acetic acid at 80°C in 68% yield. Under these mild conditions also other 3,5-substituted indoles were obtained: 3-methyl-5-benzyloxyindole (VI), 3-ethyl-5-benzyloxyindole (VII), 5-methoxytryptamine picrate (VIII) and N-acetyl-5-methoxytryptamine (Melatonin, IX).____ ___ __ _

AbstractThe synthesis of N,N-disubstituted 4-aminobutanal acetals (XV-XXII) was effected by the hydrogenation of the corresponding acetylenic analogues. N,N-Disubstituted 4-amino-2-butynal acetals (IV-XII) were prepared by the Mannich condensation of propargylaldehyde acetal, formaldehyde and the corresponding secondary amine. As an alternative route to N,N-disubstituted acetylenic aminoacetals. Bodroux-Tschitschibabin acetal synthesis was also applied in the preparation of 4-dibenzylamino-2-butynal acetal (VII).

... For the preparation of the oximes (Table 1), diethyl acetals of the corresponding aminoaldehydes were subjected to hydrolysis. The aminoaldehydes formed are unstable and polymerize readily [2,3], so we converted them to oximes without isolation....?-Dimethylaminobutyraldehyde diethylacetal was obtained from 3-dimethylaminopropylmagnesium chloride and orthoformic ester in 30% yield following the procedure described for the analogous dibutylamino derivative [5], b. p. 73-75° (6 mm), n20D 1.4217. Literature data [2]: b. p. 94-95° (11 mm), n20.5D 1.4227.

... The best approach found for the synthesis of ?-dibutylaminobutyraldehyde... involved the reaction of IV (Bu2N(CH2)3MgCl) with ethyl orthoformate [4] which yielded the diethyl acetal of ?-dibutylaminobutyraldehyde in about 60% yield. Mild acid hydrolysis afforded the free aldehyde in 86% yield. It is remarkably stable and can be distilled at atmospheric pressure....3-Dibutylamino-1-chloropropane was prepared as described by Marxer [2]....Grignard reagents from dibutylamino halides. By observing certain precautions, the above halides may easily be converted to Grignard reagents. The chief factors affecting the conversion can be enumerated as follows:

1. Moisture must be rigorously excluded. We used an apparatus in which ether from ethereal methylmagnesium iodide was directly distilled into the reaction flask. This ether was used both to help in drying the apparatus, and as a reaction solvent.

2. The magnesium should be activated with methyl iodide or ethyl bromide. We used a reaction flask with a stopcock sealed to the bottom for removing the activating solution prior to the introduction of the amino chloride.

3. The minimal amount of ether should be used in the initial phase of the reaction.

4. Stirring should be employed sparingly, if at all, until the reaction is well under way.

5. Once started, the reaction should be continued unabated until complete.

After activating the magnesium (a large excess is advantageous) with about 5 ml. of methyl iodide, employing vigorous stirring, and removal of the activating solution, a small amount of ether was distilled into the reaction flask and about 5 ml. of the amino halide added. The reaction usually started promptly, warming being rarely necessary. The reaction was kept going steadily by the addition of the amino chloride, diluted if desired with one or two volumes of ordinary anhydrous ether. The desired concentration was maintained in the reaction flask by distilling in ether from the methylmagnesium iodide flask. Moderate stirring was usually employed. The reaction was completed by heating at reflux for 0.5 hour. The yields were usually 80-85%.

These Grignard reagents are fairly insoluble in ether, and crystallize either at once, or on long standing. They are easily soluble in benzene. A normal color test (Gilman's color test I) is obtained with Michler's ketone and iodine in acetic acid. We were unable to prepare the Grignard reagents in which the halogen and nitrogen atoms were separated by 4 and 5 carbon atoms respectively.